Oral Presentation The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2017

All you need to know about the genetics of pituitary adenomas (#10)

Márta Korbonits 1
  1. Queen Mary University of London, London, United Kingdom

While just a few years ago we rarely thought about genetics when looking after pituitary patients, now this aspect of endocrinology, similar to many others, is keeping the genetic labs increasingly busy. Pituitary adenomas with genetic origin can present as part of syndrome, such as MEN1&4, Carney complex, McCune-Albright syndrome, DICER1 syndrome and SDH-related syndrome, but most often they present as isolated disease as part of Familial Isolated Pituitary Adenoma (FIPA).  In the FIPA group currently three genes have been described. (1) Heterozygous germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene lead of young-onset mostly growth hormone or mixed growth hormone/prolactin-secreting pituitary adenomas. Due to the low (~20%) penetrance almost half of the AIP mutation positive patients do not have a known family history and present as a seemingly sporadic case. (2) X-linked acrogigantism (XLAG) - duplication of the orphan G protein coupled receptor GPR101 gene, located on the X the chromosome, leads to infant-onset GH excess usually with concomitant hyperprolactinaemia. Interestingly while girls, who represent 80% of the known cases, usually have germline mutation, boys mostly have somatic mosaicism. (3) More recently a few cases of Cushing’s disease have been described with mutation in the CABLES1 (Cdk5 and Abl enzyme substrate 1) gene. The majority of the FIPA families, however, have no know genetic mutation and further studies are needed to identify the diseases causing genes in these kindreds.

But what is the point to identify the disease causing genes in patients with pituitary adenomas? In syndromic diseases it may help to search for other manifestation of the disease; characteristics of the disease may help to decide on the appropriate treatment modalities; family members can be screened and followed for early diagnosis, which is a crucial point in the successful treatment of pituitary adenomas; patients often react remarkably positively learning the genetic origin of their disease, it gives them a long-sought explanation for the “why me?” question. Finally, establishing novel pathways could lead to disease-specific treatment in the future.